SMART (simultaneous modulated accelerated radiotherapy) for locally advanced nasopharyngeal carcinomas

BACKGROUND: Concurrent chemoradiotherapy is commonly used for locally advanced nasopharyngeal carcinoma (NPC). We retrospectively analyzed the clinical outcomes of simultaneous modulated accelerated radiotherapy (SMART) with concurrent chemotherapy. METHODS: Between January 2003 and May 2005, 24 patients with stage IIB to IVB NPC underwent SMART encompassing 3 targets: gross tumor volume (GTV), high-risk subclinical disease (CTV1), and low-risk subclinical disease (CTV2). Daily fractions of 2.4, 2.15, and 1.9 Gy were delivered to GTV, CTV1, and CTV2 to a total dose of 64.8, 58.05, and 51.3 Gy in 27 fractions over 5.5 weeks, respectively. Fifteen patients received concurrent cisplatin (DDP group), and 9 received 5-fluorouracil plus cisplatin (FP group). RESULTS: With a median follow-up of 26 months (range, 17-45 months), 3-year overall and local-, regional-, and distant-progression-free survivals were 96% and 93%, 87%, and 88%, respectively. Grade 3 acute mucositis and pharyngitis were observed in 16 (67%) and 14 (59%) patients, respectively. Severe acute mucositis (100% vs 47%) and pharyngitis (100% vs 34%) were more frequently observed in the FP group than the DDP group (p < .01). CONCLUSIONS: Despite short follow-up with a small number of patients, our preliminary results demonstrated encouraging local-regional control and survival at the cost of modest increase in treatment related toxicities. The total dose and fractionation scheme of SMART used in our study is feasible with no life-threatening or fatal complications. However, the administration of fluorouracil in addition to cisplatin during SMART was associated with increased acute and late toxicities, and it should be administered with caution.     

Definitive radiotherapy with interstitial implant boost for squamous cell carcinoma of the tongue base

BACKGROUND: The purpose of this study was to examine the long-term outcome of a cohort of patients with unresected base of tongue carcinoma who received interstitial brachytherapy after comprehensive external beam radiation therapy. METHODS: Between 1983 and 2000, 122 patients with primary or recurrent squamous cell carcinoma of the oropharynx or oral cavity received interstitial brachytherapy as part of their overall management. Forty patients had primary, unresected carcinoma of the base of tongue and are the subjects of this analysis. The median age was 54 years. Fifty-four percent had T3 or T4 disease, and 70% had clinical or radiographic lymphadenopathy. Twenty-four (60%) received two to three cycles of neoadjuvant chemotherapy. The oropharynx, bilateral neck, and supraclavicular fossae were comprehensively irradiated, and the tongue base received a median external beam dose of 61.2 Gy (50-72 Gy). The primary site was then boosted with an interstitial 192Iridium implant by use of a gold-button single-strand technique and three-dimensional treatment planning. The dose rate was prescribed at 0.4 to 0.5 Gy/hr. The median implant dose was 17.4 Gy (9.6-24 Gy) and adjusted to reach a total dose to the primary tumor of 80 Gy. N2 to 3 disease was managed by a planned neck dissection performed at the time of the implant. RESULTS: The median follow-up for all patients was 56 months, and the overall survival rates were 62% at 5 years and 27% at 10 years. The actuarial primary site control was 78% at 5 years and 70% at 10 years. The overall survival and primary site control were independent of T classification, N status, or overall stage. Systemic therapy was associated with an improvement in overall survival (p = .04) and a trend toward increased primary site control with greater clinical response. There were seven documented late effects, the most frequent being grade 3 osteonecrosis (n = 2), grade 2 swallowing dysfunction (n = 2), trismus (n = 2), and chronic throat pain (n = 1). CONCLUSIONS: In an era of greatly improved dose distributions made possible by three-dimensional treatment planning and intensity-modulated radiation therapy, brachytherapy allows a highly conformal dose to be delivered in sites such as the oropharynx. If done properly, the procedure is safe and delivers a dose that is higher than what can be achieved by external beam radiation alone with the expected biologic advantages. The long-term data presented here support an approach of treating advanced tongue base lesions that includes interstitial brachytherapy as part of the overall management plan. This approach has led to a 78% rate of organ preservation at 5 years, with a 5% incidence of significant late morbidity (osteonecrosis) that has required medical management.     

Surgical treatment of squamous cell carcinoma of the base of tongue.

INTRODUCTION: Squamous cell carcinoma (SSC) of the tongue base has historically been shown to be associated with a poor prognosis. We reviewed our experience with primary surgery followed by postoperative radiation therapy (XRT) to determine the impact of our treatment protocols on outcome. METHODS: We retrospectively reviewed the records of all patients presenting to the University of Pittsburgh with previously untreated SSC of the tongue base between 1980-1997. Patients who were treated nonoperatively were excluded from analysis. Surgical excision of the primary was performed with ipsilateral neck dissection. The contralateral neck was dissected when the primary lesion was located in the midline or for clinically positive contralateral neck nodes. Postoperatively, most patients (93%) received XRT to the primary site and neck. Adjuvant chemotherapy was offered if histologic signs of aggressive behavior were identified (multiple nodes or extracapsular spread). RESULTS: Of 87 patients identified, 39 (45%) were initially seen with T1 or T2 tumors. Seventy-nine patients (91%) were initially seen with stage III or IV disease. Contralateral neck dissection was performed in 36 patients (41%). Metastatic disease was demonstrated in 84% of ipsilateral neck nodes and in 47% of contralateral neck nodes. Occult metastases were found in 61% of clinically N0 necks. Local recurrence occurred in 5 patients, regional recurrence occurred in 12 patients, and distant metastases developed in 22 patients. Overall and disease-specific survival rates at 5 years for all patients were 49% and 56%, respectively. The 5 year disease-specific survival rates for stage I, stage II, stage III, and stage IV disease were 100%, 86%, 62%, and 48%. The 5-year disease-specific survival rate was 88% for T1 lesions, 64% for T2 lesions, 58% for T3 lesions, and 30% for T4 lesions (p <.05, log-rank test). CONCLUSIONS: Surgical treatment of SCC of the tongue base is highly effective in achieving local disease control and disease-free survival for early lesions. Because both functional outcome and survival are poor after surgical treatment of advanced lesions, we now offer brachytherapy with XRT or participation in a combined chemoradiation protocol rather than primary surgical therapy to patients with advanced disease. Prospective studies are needed to compare the effect of these organ-preserving therapies with traditional combined surgery and XRT to determine the effect on functional outcome and quality of life.     

The National Cancer Data Base report on squamous cell carcinoma of the base of tongue

BACKGROUND: This study provides the largest contemporary overview of presentation, care, and outcome for base of tongue squamous cell carcinoma (SCC). METHODS: We extracted 16,188 cases from the National Cancer Data Base (NCDB). Chi-square analyses were performed on selected cross-tabulations. Observed and disease-specific survival were used to analyze outcome. RESULTS: Three-quarters had advanced-stage (III-IV) disease. Radiation therapy alone (24.5%) and combined with surgery (26.9%) were the most common treatments. Five-year observed and disease-specific survival rates were 27.8% and 40.3%, respectively. Poorer survival was significantly associated with older age, low income, and advanced-stage disease. For early-stage disease, surgery with or without irradiation had higher survival than irradiation alone. For advanced-stage disease, surgery with irradiation had the highest survival. CONCLUSIONS: Survival rates were low for base of tongue SCC, with most deaths occurring within the first 2 years. Income, stage, and age were significant prognostic factors. In this nonrandomized series, surgery with radiation therapy offered patients with advanced-stage disease the best survival.     

Role of planned neck dissection for advanced metastatic disease in tongue base or tonsil squamous cell carcinoma treated with radiotherapy

OBJECTIVE: At the conclusion of this article, the reader should be able to discuss the need for planned neck dissection for advanced cervical diseases in the tongue base and tonsil cancer after treatment with radiotherapy. BACKGROUND: In the past 5 years, we have treated patients with squamous cell carcinoma of the tonsil and tongue base with radiotherapy as the primary therapeutic modality. A planned complete neck dissection was performed on all patients with N2 or greater cervical disease regardless of response to radiotherapy. Composite resection was performed when there was persistent disease at the primary site. Although the "radiation-first" therapeutic approach for tongue base and tonsil cancer is widely accepted, the planned neck dissection for neck metastases remans controversial. The objective of the study was to determine the validity of planned neck dissection after radiotherapy for N2 disease. METHODS: Medical records of patients with primary squamous cell carcinoma of the tongue base and tonsil with neck metastasis staged N2 or greater were reviewed. Between 1994 and 1999, 36 such patients were treated with curative radiation therapy. Response was assessed 6 to 8 weeks after completion of treatment with clinical examination and CT imaging. All patients underwent planned neck dissection. We reviewed the clinical and radiographic response of neck disease to radiotherapy as it correlated with the histopathologic findings. RESULTS: Of the 36 patients, 17 had clinical and CT evidence of persistent disease. In this group, 65% had pathologically confirmed diseases at surgery. Of the 9 patients with no evidence of disease on clinical examination, negative biopsy at the primary site, and a negative CT scan, 33% (three of nine) still had residual disease in the neck dissection specimen. CONCLUSIONS: Positive findings on clinical examination and CT can predict the presence of malignancy after radiation therapy. However, a negative CT and clinical examination are limited in predicting a complete response. These data lend support to the role of planned neck dissection after radiotherapy of N2 neck disease.